Capsular polysaccharides are the primary means by which many microbial pathogens evade phagocytosis. At the present time, little is known concerning the mechanism by which capsules inhibit phagocytosis. This study will investigate the phagocytosis inhibiting properties of the capsular polysaccharide produced by Cryptococcus neoformans. The experimental model utilizes a nonencapsulated mutant that has surface receptors to which cryptococcal polysaccharide will bind. Using this systems, addition of known amounts of cryptococcal polysaccharide to the mutant strain permits experimental variation in the degree of encapsulation. The project is designed to answer four basic questions concerning phagocytosis of cryptococcus and inhibition of phagocytosis by the capsular polysaccharide: 1. What are the roles of antibody, the classical complement system, and the alternate complement system in attachment of the nonencapsulated strain to macrophages and the subsequent ingestion of the yeast? 2. Does cryptococcal polysaccharide inhibit phagocytosis by competing with these serum opsonins for their binding sites on the yeast? 3. Does the capsular polysaccharide alter either the amount of specific IgG binding to the yeast or the affinity of IgG for the yeast? 4. Can the phagocytosis inhibiting properties of cryptococcal polysaccharide be attributed to noncompetitive mechanisms such as alteration in hydrophobicity of the yeast, alteration in surface charge, or masking of cell-bound opsonins by the capsule?